Aldose reductase inhibitors constitute a class of compounds which have become widely known for their utility in preventing and treating conditions arising from complications of diabetes such as diabetic neuropathy and nephropathy. Such compounds are well known to those skilled in the art and readily identified by standard biological tests.
For example, the compound zopolrestat, 1-Phthalazineacetic acid, 3,4-dihydro4-oxo-3-[[5-(trifluoromethyl)-2-benzothiazolyl]methyl]-, is known, for example from commonly assigned U.S. Pat. No. 4,939,140 to Larson et al., (the disclosure of which is hereby incorporated by reference) together with a number of compounds related thereto, to have utility as aldose reductase inhibitors. Zopolrestat has the structure ##STR1## and, as an aldose reductase inhibitor, is useful in the treatment of the above-mentioned complications arising from diabetes mellitus.
Certain aldose reductase inhibitors have been taught for use in lowering lipid levels in mammals. See, for example, U.S. Pat. No. 4,492,706 (the disclosure of which is hereby incorporated by reference) to Kallai-sanfacon and EP 0 310 931 A2 (Ethyl Corporation).
Commonly assigned U.S. Pat. No. 5,064,830 (the disclosure of which is hereby incorporated by reference) to Going discloses the use of certain oxophthalazinyl acetic acids, including zopolrestat, for lowering of blood uric acid levels.
Commonly assigned U.S. application Ser. No. 08/059,688 discloses the use of certain aldose reductase inhibitors, including zopolrestat, for lowering blood lipid levels in humans. The disclosure notes that therapeutic utilities derive from the treatment of diseases caused by an increased level of triglycerides in the blood, such diseases include cardiovascular disorders such as thrombosis, arteriosclerosis, myocardial infarction, and angina pectoris.
Joseph R. Williamson et al., "Perspectives in Diabetes, Hyperglycemic Pseudohypoxia and Diabetic Complications", Diabetes, Vol. 42, 801-813, Jun., 1993 discloses that (FIG. 2) "Parallels between functional consequences of an increased systolic NADH/NAD.sup.+ linked to hyperglycemic pseudohypoxia in diabetic tissues and hypoxia or ischemia in myocardial tissue."